Uterine infections and infections of the cervix, vagina and vulva commonly occur in human beings and domestic animals, especially following birth. Typical infecting organisms of the endometrium (uterine mucosa) and contiguous mucosal surfaces in the lower genital tract include, for example, .beta.-hemolytic streptococci, Candida albicans, Klebsiella pneumoniae, coliform bacteria including Escherichia coli, Corynebacterium pyogenes and C. vaginale, various Campylobacter or Trichomonas species such as T. vaginalis, and the like. Even mild vaginitis is uncomfortable, and even where endometritis is mild, the impact on fertility can be substantial. Fertility depression and aberrations of the estrous cycle are typical symptoms. Acute infections can lead to complications; acute endometritis and metritis, for example, can eventually involve all organ layers and cause abortion, extensive hemorrhage, necrosis, abscesses, peritonitis, toxemia or septicemia, and death.
The normal nonpregnant uterus is endowed with a high degree of resistance to infection, and even in the case of specific genital diseases such as brucellosis, trichomoniasis, and Campylobacter infection, is ordinarily incapable of supporting bacterial growth or the persistence of bacteria for any extended period. Normal antibody production plays a role in this resistance, but, more importantly, bacterial clearance from the endometrium and phagocytic response to bacteria are enhanced by estrogen and suppressed by progesterone (Jubb, K. V. F., et al., Pathology of Domestic Animals, 3rd ed., vol. 3, Academic Press, New York, 1985, pages 330-332).
The uterus under the influence of progesterone (which includes the pregnant uterus), on the other hand, is very susceptible to nonspecific bacteria and often becomes infected. Some postpartum metritis is a continuation and exaggeration of a gestational uterine infection, but most puerperal infections of the uterus are analogous to wound infections, with organisms entering via the cervix, sometimes in conjunction with obstetrical manipulations. It has been stated, for example, that probably all mares have uterine infections by streptococci within 1 to 3 days after parturition (ibid.).
Ruptures and/or infections of the vagina and vulva are frequently acquired as parturient injuries. Vaginitis that is sexually transmitted or transmitted by other means is even more common. Vaginitis is generally divided into three types: yeast infection (ordinarily Candida albicans), trichomonas (typically T. vaginalis), and "nonspecific" vaginitis caused by other organisms. Mixed (polymicrobial) infections may also occur.
The outcome of lower genital tract infection is determined by the number and virulence of invading organisms as well as by the environment within the uterus and birth canal and the health of the female. Infections may be "subclinical," where the infection is not directly evident by palpation or visual gynecological examination, or "clinical," which is diagnosed by the presence of visually detectable alterations in the cervix, organ enlargements and other changes, tenderness and pain, discharges, and sometimes foul odors. The endometrium may be congested and swollen, exhibiting small hemorrhages and a prominent leukocytic infiltration; vaginal and vulvar itching may be troublesome. Elevated levels of white cells in response to the infection is often observed, and milk production in postpartum females can be depressed.
Some milder cases of endometritis recover health and fertility spontaneously. Many acute cases, on the other hand, can lead to complications such as chronic endometritis, uterine abscess, parametritis, and the like, and many animal cases are fatal in spite of therapy. Treatments for infection include infusions of antibiotics into the birth canal and uterus, which can be irritating, or systemic administration of antibiotics. Penicillin is the appropriate drug for most streptococcal infections, but enterococci, E. coli, Bacteroides fragilis, and other gram-negative bacilli often recovered in puerperal infections are relatively unresponsive to it. As a consequence, a combination of drugs is preferable to penicillin alone, such as streptomycin or kanamycin in combination with penicillin.
Treatment is commonly instituted prior to identification of the specific causative organism or organisms, and antibiotic dosage alterations or drug changes may be necessary after identification of organisms in culture. It is important at the outset to select an antimicrobial which offers the greatest range of efficacy against an array of pathogens that could be causing infection. Use of broad-spectrum antibiotics can, however, lead to tolerance problems and allergies. Antibiotics systemically administered to a nursing mother can contaminate her milk and alter the intestinal flora and have other deleterious effects on the suckling offspring, and, in the case of cow's milk, can render it unfit for consumption or use in processing into cheese or yogurt. Some systemic antibiotic therapies are not recommended for pregnant women, especially during their first trimester. And in veterinary practice, the cost of antibiotics can be prohibitive.
Fungicides are employed to treat yeast infections; for Candida vaginitis, intra-vaginal nystatin is typically employed. Unfortunately, antibiotic therapy can increase susceptibility to vaginal candidiasis (Cecil's Textbook of Medicine, 18th ed., W.B. Saunders Co., 1988, pages 1704 to 1706), so that treatment of one genital tract infection can exacerbate another. Trichomonad vaginitis is treated with nitroimidazoles, but there is evidence that these are weakly carcinogenic in certain animal systems (ibid.).
It would be desirable to have alternate and adjunct methods for the treatment and prevention of lower genital tract microbial infections in females, such as postpartum infections and vaginitis.